ABSTRACT

1
ABSTRACT

• Purpose. To investigate why infantile nystagmus
  syndrome (INS) patients often complain that they
  are slow to see. Static measures of visual
  function (e.g., visual acuities) do not measure
  normal dynamic demands on visual function.
  Time-sensitive measures are required to more
  fully measure and understand visual function. We
  investigated the dynamic properties of INS on
  saccadic latency (Ls) and target acquisition time
  (Lt)new aspects of visual function. Our
  behavioral ocular motor system (OMS) model
  predicted stimulus-based effects on target
  acquisition time in INS. Measurements of the
  dynamics of INS foveation in patient responses to
  changes in target position were used to evaluate
  both the patient complaint and model predictions.
• Methods. We used the responses of 4 INS subjects
  with different INS waveforms to test the models
  predictions. Infrared reflection was used for 1
  INS subject, high-speed digital video for 3. We
  analyzed human responses to large and small
  target-step stimuli. We evaluated time within
  the cycle (Tc), normalized Tc (Tc), initial
  orbital position (Po), saccade amplitude, initial
  retinal error (ei), and final retinal error (ef).
  Ocular motor simulations were performed in MATLAB
  Simulink and the analysis was performed in MATLAB
  using OMLAB software.
• Results. Ls was a fixed value that was typically
  higher than normal. For Lt, Tc was the most
  influential factor for each waveform type. Model
  outputs accurately simulated human data.
  Refixation strategies depended on the size of the
  required position change and used slow and fast
  nystagmus phases, catch-up saccades, or
  combinations of them. These strategies allowed
  effective foveation after target movement,
  sometimes producing increased Lt.
• Conclusions. Saccades disrupt the OMS ability to
  accurately calculate saccade amplitude and
  refoveate. Idiosyncratic variations in Ls occur
  among INS subjects. OMS model simulations
  demonstrated this emergent behavior this robust
  model can be used to predict and reinforce data
  analysis in future research.
• Nothing to Disclose

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TR PROCEDUREDiscovery-Hypothesis-Demonstration-T
rial-INSAN Therapy

• 1978 Secondary effects of Kestenbaum surgery
  discovered
• 1979 Secondary effects of Kestenbaum surgery
  reported
• 1979 TR surgery hypothesized
• 1992 Achiasmatic Belgian sheepdog model of INS
  found
• 1998 Horizontal TR procedure demonstrated on
  sheepdog
• 1998 Vertical TR procedure demonstrated on
  sheepdog
• 1999 Positive TR procedure results in INS and
  SSN reported
• 1999 Proprioceptive hypothesis for TR procedure
  advanced
• 2000 NEI sponsored masked-data clinical trial
  begun
• 2002 Proprioceptive hypothesis for TR procedure
  supported
• 2003 Positive phase-1 (10 adults) clinical trial
  results reported
• 2003 First attempted TR procedure for APN
• 2004 Positive phase-2 (5 children) clinical
  trial results reported
• 2004 Positive TR procedure results in APN
  reported
• 2005 Demonstration that TR procedure affects
  only small signals
• 2005 Demonstration that TR procedure broadens
  the null region
• 2006 Positive TR procedure results in acquired
  DBN reported

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BACKGROUND

• TR has been reported to increase visual acuities
  of patients with infantile nystagmus syndrome
  (INS), asymmetric, (a)periodic alternating
  nystagmus (APAN), acquired pendular (APN) and
  downbeat (DPN) nystagmus, and to reduce
  oscillopsia in the latter two.
• The broadening of the NAFX peak post-therapy
  demonstrated the need to assess pre-therapy
  waveform quality and visual acuity at different
  gaze angles.
• INS patients complain that they are slow to see.

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QUESTIONS

• What causes the variable impression of being
  slow to see?
• Does INS lengthen saccadic reaction time?
• Does INS lengthen target acquisition time?
• If any of the above are true, what target
  criteria affect the changes and by what
  mechanism(s)?
• Is there a dynamic measure of visual function
  that should be assessed in INS?

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HYPOTHESES

• Small saccadic latency increases are not the
  cause of the slow-to-see phenomenon.
• The timing of the target jump within an INS cycle
  will adversely affect the total target
  acquisition time.

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METHODS

• Ocular motor simulations using a behavioral OMS
  model were performed in MATLAB Simulink and the
  saccadic latency analysis was performed in MATLAB
  using OMtools software.
• High-speed digital video and infrared reflection
  systems were used to measure the eye movements
  (fixation and saccades) of four patients with
  INS.
• Eye movement data were calibrated and analyzed
  for the fixating eye. Stimulus timing, orbital
  position, and retinal errors were examined.

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METHODS
Ls - Saccadic Latency Lt - Target Acquisition
Time Tc - Stimulus Time in INS Cycle
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OCULAR MOTOR SYSTEM MODEL
2004, Jacobs et al.
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MODEL PREDICTIONS
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MODEL PREDICTIONS
Different Target Timings
Counter-intuitive? Target jumps during still
foveation periods have longer target acquisition
time
Its the intrinsic saccades that matter!!
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RESULTS Saccadic Latencies
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RESULTS Target Acquisition Times
Large Steps
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RESULTS Target Acquisition Times
Large Steps
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RESULTS Target Acquisition Times
Large Steps
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RESULTS Target Acquisition Times
Small Steps
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RESULTS Target Acquisition Times
Small Steps (Same results for large steps)
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RESULTS Foveating Strategy
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RESULTS Foveating Strategy
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RESULTS Foveating Strategy
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RESULTS Foveating Strategy
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RESULTS Foveating Strategy
Lt1s
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RESULTS Foveating Strategy
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RESULTS Foveating Strategy
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RESULTS Foveating Strategy
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CONCLUSIONS

• Although saccadic latency appears somewhat
  lengthened in INS, the amount is insufficient to
  cause the slow-to-see impression.
• The variable slow-to-see impression is caused
  by the interaction of the time of a target jump
  and the intrinsic saccades generated as part of
  INS waveforms.
• Target jumps occurring near intrinsic saccades
  result in inaccurate saccades and lengthen the
  total target acquisition time far beyond saccadic
  latencies and result in the real phenomenon of
  being slow-to-see.

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CONCLUSIONS

• The Behavioral OMS Model
• 1. Accurately predicted increases in total target
  acquisition time in the presence of INS
  waveforms.
• 2. Demonstrated that it was the interaction
  between intrinsic waveform saccades and the
  required voluntary refixation saccade that
  resulted in the increased target acquisition time.

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CONCLUSIONS

• Static measures of visual function (i.e.,
  primary-position and lateral gaze visual acuity
  measurements) are insufficient measures of
  important visual function variables like target
  acquisition time.
• Individuals with INS should also be tested for
  target acquisition time as part of their visual
  function assessment.